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Genetic Screens

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...

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Updated: Feb 19, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER

Published on: June 23, 2012

High-throughput, image-based screening of pooled genetic-variant libraries.

George Emanuel^1,2,3, Jeffrey R Moffitt^1,3, Xiaowei Zhuang^1,3

¹Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.

|October 31, 2017

Summary

We developed a high-throughput screening method for imaging cell genotypes and phenotypes. This technique successfully identified improved fluorescent protein variants from a large library.

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Area of Science:

Cell biology
Genetics
Biotechnology

Background:

High-throughput screening is crucial for biological discovery.
Current methods often lack the ability to link genotype with phenotype at the single-cell level.

Purpose of the Study:

To develop a novel high-throughput screening method for simultaneous imaging of diverse genotypes and phenotypes in individual cells.
To demonstrate the utility of this method in identifying improved biological variants.

Main Methods:

Genotyping was achieved by introducing barcoded genetic variants into pooled cell libraries.
Massively multiplexed fluorescence in situ hybridization was used for barcode readout.
Image-based screening allowed for phenotype assessment.

Main Results:

The method successfully imaged diverse genotypes and phenotypes in individual cells.
We identified novel variants of the fluorescent protein YFAST with enhanced brightness and photostability.
Screening was performed on a library of 60,000 variants.

Conclusions:

This image-based pooled screening approach enables efficient discovery of functional genetic variants.
The developed method significantly advances high-throughput biological screening capabilities.